Learn more about what treatments are on the rise for plaque psoriasis, the latest management advice and what trends are shaping the future of the disease. 

The changing treatment landscape of plaque psoriasis

Continuing research on the pathogenesis of acne has yielded a new understanding of underlying molecular and cellular pathways, suggesting new targets for therapeutic intervention, says Ichiro Kurokawa, MD, director, Department of Dermatology, Meiwa Hospital, and clinical educational professor, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan, in collaboration with Keisuke Nakase, PhD, assistant professor, Department of Microbiology, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan.

The information on these advances is summarized in a recent article1 written by Kurokawa and Nakase. The authors review recent findings on the pathogenesis of acne, discuss novel treatments, and propose future therapeutic strategies. With the need for additional treatments for severe acne, Kurokawa tells 

that findings from immunological studies are of interest as they suggest the potential to use immunity induction therapy with antibodies.

“The future treatment for severe acne will involve biologic therapies targeting interleukin (IL)-1α, IL-1β, IL-6, tumor necrosis factor (TNF)-α, and transforming growth factor (TGF)-β,” he says. In particular, these pro-inflammatory cytokines are involved in the development of scar formation, which is the most refractory complication of severe acne. In addition, TNF-α promotes lipogenesis in human sebocytes,” says Kurokawa.

“Treatments that enable wound healing are also of interest as a therapeutic intervention to prevent permanent scarring in patients who suffer from severe acne,” he adds.

The discussion of recent findings on acne pathogenesis is divided into sections reviewing research pertaining to sebaceous gland biology, sebum, genetics, keratinization, hair cycles, immunology, bacteriology, and wound healing. Findings from these studies suggest numerous novel potential treatments.

Kurokawa explains that insulin growth factor (IGF)-1 is involved in acne pathogenesis through stimulation of lipid formation. In addition, research investigating genetic associations with acne development implicates the involvement of genes in the IGF family as well as in the melanocortin receptor and peroxisome proliferator-activated receptor (PPAR) families among others.

Kurokawa and Nakase note that while existing antimicrobial agents used for treating acne are believed to have benefits for both their effects on 

(C acnes) and anti-inflammatory activity, the search for alternatives continues due to concern over the emergence of bacterial resistance with antibiotic overuse. Vaccination strategies for eradicating 

and preventing its overgrowth show promise.

induces production of pro-inflammatory cytokines. Complete suppression of acne inflammation would likely mean combining these vaccinations with monoclonal antibody agents able to block the pro-inflammatory cytokines,” Kurokawa says.

Although there has been limited study of hair cycles in acne and a lack of research into keratin expression in the hair cycle in acne lesions, available evidence shows a shift in the hair cycle from anagen to telogen or catagen phases, according to the authors.

Kurokawa and Nakase speculate that progenitor cells in the junctional zone might differentiate towards the infundibulum and sebaceous duct cells rather than towards the lower portion of the hair follicles.

“The sebaceous gland with hypercornification in the sebaceous duct is usually atrophic without the outer root sheath below the opening of orifice of sebaceous gland,” Kurokawa says.

The authors also review novel acne therapies being used in Japan that show encouraging results for the treating both nodulocystic acne and perifolliculitis capitis abscedens et suffodiens, a related treatment-refractory disorder.

Kampo is a traditional Japanese herbal medicine using Saireito. While it is used in combination with topical benzoyl peroxide, oral antimicrobial agents, and local steroid injections, there is biological plausibility for benefit of Saireito, according to the article’s authors.

“Basic research studies are needed to determine the mechanisms by which Saireito modulates acne pathogenesis, but there is evidence that its activities include effects on endogenous corticosteroids, inflammation, reactive oxygen species, coagulation, macrophages, neutrophils, and endothelial cells,” Kurokawa says.

Other treatments used for severe acne in Japan include Jyumihaidokuto and Keigairengyoto. Jyumihaidokuto contains Bokusoku, an extract from 

that has been shown to inhibit testosterone-induced sebum synthesis. Keigairengyoto has both an antibacterial effect on 

Kurokawa, MD and Nakase, PhD report no relevant disclosures.

1. Kurokawa I, Nakase K. Recent advances in understanding and managing acne. 

Articles

Acne research delineating molecular and cellular pathogenic pathways gives insight into new therapeutic targets. According to a recent review, biologics and other therapies that modulate scar formation and wound healing will have value for treating severe acne.

Immunity Induction Therapy with Antibodies, Wound-Healing Therapies Show Potential 

Podcasts

Esther Freeman, MD, PhD, details how her and her fellow colleagues banded together to create a COVID-19 dermatology registry in just eight days. The registry has since seen over 1,000 submissions from frontline clinicians located in 40 countries, helping to identify and diagnose active COVID-19 through submitted skin findings.

The Cutaneous Connection- Episode 15: Building a COVID-19 Dermatology Database

Allergan Aesthetics, an AbbVie company, announces the company has entered into a warrant agreement to acquire Cypris Medical, a private medical device company, according to a press release from Allergan.

After the completion of a clinical trial that will begin in 2021, Allergan will have the option to acquire Cypris Medical and its Xact device. The clinical trial will investigate the safety and efficacy of Xact in neck lifts and treating midface descent.

"As the market leader in facial aesthetics, Allergan Aesthetics is the ideal partner to lead the advancement and continued development of Xact," said Dan Holton, president and CEO of Cypris Medical. "We share the same vision with respect to product safety, efficacy and data-driven innovation which allow us to offer plastic surgeons and patients new options for aesthetic medicine."

The Xact is a minimally invasive facelift device that works by allowing lifting and suturing of the superficial muscular aponeurotic system (SMAS), the same tissue mobilized in a surgical facelift procedure. This technology provides patients with surgery-like results in the office with minimal to no downtime, according to the press release.

"As a global leader in aesthetics, we are proud to support the research of an innovative device that complements our iconic portfolio of non-invasive treatment options like Botox Cosmetic and our Juvéderm collection of fillers," said Carrie Strom, senior vice president of AbbVie and president of Global Allergan Aesthetics. "We know there is continued unmet need for minimally-invasive procedures for midface descent, and Xact affords us the ability to create a new alternative for our customers so they can continue to offer leading-edge treatments to patients."

1. Allergan Aesthetics Enters Into Option to Acquire Cypris Medical. (2021, January 12). Retrieved January 13, 2021, from https://news.abbvie.com/news/press-releases/allergan-aesthetics-enters-into-option-to-acquire-cypris-medical.htm?view_id=5591

Allergan Aesthetics has entered into a warrant agreement that will give the company an option to acquire Cypris Medical following the completion of a clinical trial evaluating Cypris’ Xact device. 

Allergan Aesthetics to Acquire Cypris Medical in Warrant Agreement

New topicals, narrow-spectrum antibiotics, and research on the skin microbiome are paving the way for the future of acne treatment, according to Jenna Lester, MD.

In a presentation at the Orlando Dermatology, Aesthetic & Surgical Conference (ODAC) Preconference Sneak Peek Inflammatory Diseases Symposium held virtually in December 2020, Lester provided an overview of promising treatments and therapies for patients with acne vulgaris. She is an assistant professor in the Department of Dermatology at University of California, San Francisco (UCSF), Health and founder and director of UCSF Skin of Color Clinic.

The US Food and Drug Administration (FDA) approved trifarotene (Aklief, Galderma), a topical retinoid for treatment of facial and truncal acne, in May 2020.

 Retinoids such as trifarotene, which bind to the retinoic acid receptor (RAR), have 3 isoforms: RARα, RARβ, and RARγ. Trifarotene is unique; it is the only topical retinoid that selectively targets RARγ, the most common RAR found in the skin. The drug is also the first topical treatment studied and proven to treat both facial (forehead, cheeks, nose, and chin) and truncal (chest, shoulders, and back) acne, according a press release from Galderma.

In a 52-week open-label comparative study, 455 patients were given trifarotene. Data showed that the agent was well tolerated among participants. The most common adverse effects included pruritus, irritation, and sunburn, all of which occurred most frequently within the first 3 months of treatment. Results showed that at 52 weeks, more than half (57.9%) of patients achieved treatment success at 52 weeks. Quality of life also improved over that time frame, according to the data.

“When I’m counseling about acne topical treatments, I’m usually telling people how things will improve in 3-month cycles. By 6 months, if things aren’t better, I might decide to increase strengths of tretinoin or move some things around,” Lester said. “But for trifarotene, it seems that the efficacy is experienced at the highest percentages at about a year. So, for patients who may not tolerate waiting that long, this may not be the best medication.…However, the trickle effects of it really can’t be ignored.”

In August 2020, clascoterone cream (Winlevi; Cassiopea), received FDA approval for the treatment of acne in patients 12 years and older.

 Clascoterone is an androgen receptor antagonist that specifically competes against androgens such as dihydrotestosterone by binding to the androgen receptors located in hair follicles and sebaceous glands. This mechanism of action helps decrease production of sebum and inhibits activation of inflammatory pathways and proinflammatory cytokine synthesis. 

In 2 randomized, vehicle-controlled, double-blind studies investigating clascoterone cream in 1440 males and nonpregnant females (all White), results showed a reduction in inflammatory and noninflammatory lesions. Overall, this topical was well tolerated, according to Lester.

Minocycline (Amzeeq; Vyne Therapeutics) was approved by the FDA in October 2019 for the treatment of nonnodular inflammatory moderate-to-severe acne in patients 9 years and older.

 A 4% minocycline foam falls under the tetracycline class of antibiotics, Lester said.

Results of a randomized, double-blind, vehicle-controlled study investigating 4% minocycline foam in 1488 patients showed an improvement in inflammatory lesions and revealed that 30.8% of patients achieved treatment success (Investigator Global Assessment of 0 or 1 and an improvement of 2 grades by week 12).

Lester adds that, compared with trifarotene, topical minocycline demonstrates a faster efficacy profile. “One of the reasons that this was an ideal medication to convert into a topical treatment is [that] because of the tetracyclines, minocycline has the least resistance and the most favorable [adverse] effects profile when comparing [with] doxycycline or tetracycline,” she said. “However, we know that there is potential for significant [adverse] effects, particularly discoloration and acne scarring, when taken systemically. With the increase in resistance to topical clindamycin and erythromycin, our setting is really prime for incorporating another topical antibiotic medication into our acne regimen.”

Lester also recommends the use of oral antibiotics such as sarecycline (Seysara; Almirall), a novel narrow-spectrum tetracycline class antibiotic approved by the FDA in 2018 to treat acne in patients 9 years and older.

The drug possesses a stable C-7 moiety and works by targeting 

)while having little activity against gram-negative organisms and intestinal microflora, Lester said. Protecting the microflora decreases short-chain fatty acids, which can be anti-inflammatory. It also prevents gastrointestinal distress, which, when disrupted, could make patients less likely to stay on the medication, she added.

In a clinical study, results showed that sarecycline performed well for facial, back, and chest acne, according to Lester. “We all are trying in dermatology to be better antibiotic stewards. If you’re not already recommending [sarecycline] for your patients, this is an excellent option,” she said. “It is a very narrow-spectrum tetracycline, and narrow-spectrum medications are what we’re aiming for in terms of being good antibiotic stewards in guarding against resistant bacteria.”

Lester reemphasizes the importance of protecting the skin and gut microbiome, which is made up of more than 1000 commensal species that occupy spaces that pathogenic bacteria otherwise would occupy.

 are associated with acne, whereas others are associated with healthy skin. Some phylotypes also attack unhealthy types of the acne. In addition, gut organisms can influence glycemic control, tissue lipid content, and inflammation, which can have a direct impact on skin disease.

Few clinical trials look at topical probiotics for prevention and treatment of skin conditions except in atopic dermatitis, according to Lester. The results of one study found that consuming 

 was just as effective as taking minocycline, whereas other study findings showed a decrease in inflammatory lesions.

Despite the promise of these findings, Lester said, more research must be done on the skin and gut microbiome and how they influence inflammatory skin diseases such as acne.

1. Lester J. Acne: changing practices in a changing clinical landscape. Presented at: Orlando Dermatology Aesthetic and Clinical 2021 Preconference Sneak Peek Inflammatory Diseases Symposium; December 3, 2020; virtual. 

Topicals and oral antibiotics, as well as research on the skin microbiome, are paving the way for the future of acne treatment, according to a recent presentation at the 2020 ODAC Pre-Conference Inflammatory Diseases Symposium.

Next-Generation Therapies and Approaches Will Advance Acne Treatment

The shift to telehealth visits during the height of the first wave of the COVID-19 pandemic effected noteworthy changes in the sociodemographic and clinical characteristics of patients presenting for care at a tertiary referral center, according to a recently published study.

The findings provide insights for understanding the impact of the pandemic on dermatology and, moving forward, for determining which patient populations may benefit most from access to teledermatology and how to optimize its delivery, says Avery LaChance, MD, MPH, director of Health Policy and Advocacy, Brigham and Women’s Hospital Department of Dermatology, and instructor in Dermatology, Harvard Medical School, Boston, Mass.

“It is essential that we study how the rapid expansion of telehealth throughout the pandemic impacted our patients and the practice of medicine,” says LaChance. “As a medical community, we should seek to learn as much as possible about how we can optimize telemedicine to improve patient access to dermatologic care.”

To evaluate the impact of the transition to telehealth on the practice of dermatology, LaChance and colleagues at the University of Massachusetts Department of Dermatology conducted a retrospective chart review comparing the characteristics of patients seen for in-person visits in April 2019 versus by telehealth in April 2020. The in-person cohort included 1565 patients while 767 patients were seen via telehealth during the pandemic period.

“In April, Massachusetts was recommending that all non-emergent health care be provided by telehealth. [Increased access to in-person care opened up in late May/early June.] Focusing on the month of April gave us an opportunity to investigate which patient populations were seeking out and accessing telehealth during this unique time period,” says LaChance.

She adds, “We felt that only patients who believed they would truly derive benefit from telehealth, such as those who felt their care could not wait, their condition could be adequately managed by telehealth, or who found this mode of care to be an acceptable alternative to an in-person visit, would have transitioned to virtual care during this period of time.”

Statistically significant differences identified in the two patient populations show that patients seen by telehealth were significantly younger, more likely to live out-of-state, and more diverse racially, ethnically, and linguistically. Online visits included a higher proportion of Medicaid recipients but a lower proportion of Medicare patients than the in-office cohort.

Virtual visits for inflammatory dermatoses and hair disorders accounted for higher percentages of the primary diagnoses in the teledermatology cohort. However, skin cancer and other neoplastic disorders were most common among study group patients seen in-office.

Commenting on the findings, LaChance says that the proportional increase in patients presenting for hair disorders is interesting considering a study reporting that dermatologists believe examinations for alopecia are less amenable to teledermatology.

“Hair loss is a very emotionally charged disease. Affected patients may have felt very strongly about keeping their appointment during the pandemic,” she says. “Another factor may be that certain hair loss disorders, such as telogen effluvium, which is a type of stress-induced hair loss, have increased throughout the pandemic, possibly contributing to this finding.”

LaChance says she and her colleagues “were happy to see” the uptake of telehealth by Medicaid patients. The investigators credit the broad insurance coverage of telehealth during the pandemic across multiple modalities and different types of technologies in facilitating telehealth access for patients across all backgrounds. Additionally, she notes that patients with Medicaid or in a low income bracket often face social pressures that may limit their access to in-person visits.

“The flexibility and convenience afforded by telehealth may offset the influence of a potential ‘digital divide’ and help explain the increased percentage of Medicaid patients seen by telehealth,” she says. “This is echoed by our findings in another study showing decreased no-show rates for teledermatology versus in-person visits with the most dramatic difference seen among minority patients.”

“We need to do the heavy lifting and conduct more research to understand how patients in all demographic and socioeconomic groups interface with technology and what can be done to ensure equitable access to telehealth now and moving forward,” says LaChance.

As in-person care has opened up, LaChance says that the characteristics of the patient she is seeing virtually match those of the study’s teledermatology cohort. The telehealth clinic patients are generally younger, face numerous social stressors, and have inflammatory diseases (versus concerning lesions).

“Patients and doctors together are considering multiple factors to select the mode of care that is best for each patient individually. We are improving access to care and the patient experience,” she says.

Ongoing research is focusing on defining the current digital divide in the dermatology patient population, evaluating patient satisfaction between telehealth and in-person visits for different conditions, and understanding how telehealth has improved access to care for different patient populations. Recognizing that patient populations differ depending on practice characteristics, LaChance is hopeful that others practicing in different settings and geographic locations will conduct similar research to gain a more comprehensive picture of which patient populations and disease states would benefit from continued access to teledermatology.

She and her colleagues are using their findings to advocate for legislation to ensure broad telehealth coverage in Massachusetts.

“To date, a lot of expanded coverage for telehealth is afforded by emergency legislation and executive orders at the state and federal levels,” she adds. “Legislation is needed to ensure patients continue to have broad access to telehealth coverage now and in the future.

Physicians must advocate for our patients to influence the next wave of telehealth legislation so we can maintain equitable access to this mode of care for all patients.”

1. Krueger S, Leonard N, Modest N, et al. Identifying Trends in Patient Characteristics and Visit Details During the Transition to Teledermatology: Experience at a Single Tertiary Referral Center. 

. 2020 Nov 27:S0190- 9622(20)33084-X. Epub ahead of print.

2. Franciosi EB, Tan AJ, Kassamali B, et al. Understanding the Impact of Teledermatology on No-Show Rates and Healthcare Accessibility: A Retrospective Chart Review. 

. 2020 Sep 11:S0190-9622(20)32604-9. Epub ahead of print

A retrospective study shows significant differences in the characteristics of patients seen by telehealth during the COVID-19 pandemic versus those seen during in-office visits 1 year earlier.

COVID-19-related telehealth broadens patient population 

John Jesitus is a medical writer based in Westminster, CO.

 showing an association between finasteride use and psychological adverse events (AEs) including suicidality suggests that dermatologists should weigh benefits and risks carefully when considering finasteride for certain patients with hair loss, according to one expert.

Based on the study, the characteristics of finasteride may precipitate or potentiate psychological morbidities including suicidality specifically in patients with alopecia who are less than 45 years of age, says Roger S. Ho, MD, MS, MPH. He is director of resident education and associate professor in the Ronald O. Perelman Department of Dermatology at New York University Grossman School of Medicine, New York, N.Y. Ho was not involved with the study but wrote an accompanying editorial on the topic.

“While a definitive causal association has not yet been established, dermatologists should take into consideration this potential signal and conduct a detailed, personalized risk-benefit assessment with the patient before each prescription of finasteride for our younger alopecia population,” says Ho.

Study1 authors Nguyen et al. used disproportionality analysis (specifically, case-noncase design) to detect signals of adverse finasteride

reactions of interest reported in the World Health Organization’s global VigiBase database as of June 2019. Researchers identified 3282 adverse events (AEs) of interest, including 2926 reports of psychological AEs and 356 reports of suicidality. Nearly all cases involved male patients, and 70.9% of involved patients with age data available were 18 to 44 years old.

Researchers identified significant disproportionality signals for both psychological AEs (reporting odds ratio (ROR) 4.33; 95% confidence interval (CI) 4.17-4.49, and suicidality (ROR, 1.63; 95% CI 1.47-1.81) in finasteride users. Investigators found no signals for attempted or completed suicide.

In sensitivity analyses stratified by indication and age, patients younger than 45 years (ROR 3.47; 95% CI 2.90-4.15) and those with alopecia (ROR 2.06; 95% CI 1.81-2.34) had significant disproportionality signals for suicide compared to patients in the database using other alopecia drugs such as minoxidil. No suicidality signals appeared among older men who presumably took finasteride for benign prostatic hyperplasia.

According to Nguyen et al., the findings raise concern that younger men with alopecia may be especially at risk for suicidality compared with the general population. “Taken together,” they

wrote, “our findings suggest that the disproportional reporting of suicidality and psychological AEs in association with finasteride use could potentially be attributed to unique characteristics of the drug in young patients with alopecia.”

For example, psychological AEs could stem from the possibility that the persistent sexual dysfunction (after discontinuation of treatment) that has been associated with finasteride takes a greater toll on younger patients who had used the drug to treat a non-urological condition.

The disproportionality signals for psychological AEs and suicide among finasteride users also may stem partly from reporting bias. Sensitivity analyses showed disproportional reporting of finasteride-associated suicidality after 2012, a year that drew significant attention to a possible link between finasteride and these AEs.

Ho points out the signals for suicidality and psychological AEs identified by Nguyen et al. for finasteride only serve to stimulate further large-scale prospective pharmacoepidemiologic studies designed specifically to further evaluate these potential AEs in young patients using the drug for androgenetic alopecia. “They should not be mistaken as proof that there is a causal association between the two, as the study had some inherent biases, in particular a reporting bias due to stimulated reporting in the database,” he says.

Dr. Ho reports no relevant financial interests.

Nguyen DD, Marchese M, Cone EB, et al. Investigation of suicidality and psychological adverse events in patients treated with finasteride [published online before print, November 11, 2020]. 

. 2020 Nov 11:e203385. doi: 10.1001/jamadermatol.2020.3385.

HoRS. Ongoing concerns regarding finasteride for the treatment of male-pattern androgenetic alopecia [published online before print, November 11, 2020]. J

2020;10.1001/jamadermatol.2020.3384. doi:10.1001/ jamadermatol.2020.3384.

A recent study shows an association between finasteride use and psychological adverse events (AEs) including suicidality. Dermatologists should weigh benefits and risks carefully when considering finasteride for certain patients with hair loss, according to one expert.

Study examines finasteride risks for younger males 

writes about seven uncommon ingredients that could possibly help treat acne and provides a thorough guide to laser treatments for the skin and hair. Meanwhile, 

reveals how to take care of wet hair to avoid breakage and dives into the latest skin treatments available for darker skin types. Finally, 

features one psoriasis patient’s skincare routine and 

explains what everyone should know before getting dermal fillers.

7 Lesser-Known Acne-Fighting Ingredients You Haven't Tried

The Complete Guide to Laser Treatments for Hair and Skin

How to Care for Wet Hair to Avoid Breakage

These Skin Treatments Are *Finally* Available for Darker Skin Tones

I Have Psoriasis, and This Skincare Routine Keeps My Flare-Ups at Bay

10 Things to Know Before Trying Dermal Fillers

This week’s edition of The Mainstream Patient features stories on acne treatment alternatives, dermal fillers, skincare regimens for psoriasis, wet hair care, laser treatments, plus more. 

The Mainstream Patient: January 11, 2021

Poll

POLL: When do you expect in-person conferences to resume?

The latest content from our January issue;

A brand new edition of The Mainstream Patient;

Check back with our website frequently so you don’t miss any of the latest dermatology news.

A glimpse at what to expect from Dermatology Times this week.

What’s new on Dermatology Times: January 11-15

In case you missed it, some of this week’s featured content about expanding systemic therapies for psoriasis, new positive results from a phase 2 study investigating DAXI, guidance on COVID-19 vaccine side effects in dermal filler patients, new American Academy of Dermatology (AAD) and National Psoriasis Foundation (NPF) guidelines for psoriasis, plus more.

POLL: Do you incorporate antibiotics into your patients' acne treatment plan?

This week’s edition of The Mainstream Patient features stories on milia, alcohol in skincare, body acne, silicone sheet masks, plus more.

Chief Medical Editor Zoe Diana Draelos, MD, discusses the challenges COVID-19 induces on the skin including chapped lips, maskne and dry hands from excessive hand washing.

Saving the world through pharmaceutical innovation

The COVID-19 vaccine, and the speed at which it was developed, is the medical breakthrough of our lifetimes.

Can doctors be expert witnesses against non-physicians?

In this month's Legal Eagle article, David J. Goldberg, MD, JD, examines the legality of whether physicians can be used as an expert witness against non-physicians.

New AAD-NPF psoriasis guidelines mark changes

New AAD-NPF guidelines focus on biologics, topical therapy, systemic non-biological therapies, management of pediatric patients, use of phototherapy and comorbidities.

DAXI demonstrates positive results in phase 2 study

Revance Therapeutics announces positive results from its phase 2 multicenter, open-label study investigating DaxibotulinumtoxinA (DAXI) as an injectable treatment for glabellar lines, lateral canthal lines and dynamic forehead lines.

Guidance issued for COVID-19 vaccine side effects in dermal filler patients

A new guidance from the American Society for Dermatologic Surgery (ASDS) has been released regarding side effects from the SARS-CoV-2 mRNA vaccine on dermal fillers.

Expanding line of therapeutic agents for psoriasis

Several systemic therapies are available for the treatment of patients with moderate to severe psoriasis. Continued research has further elucidated the immunopathogenesis of the disease, leading to the development of novel biologic agents that are proving to more effectively and safely address moderate to severe psoriatic lesions.

ICYMI, some of the content featured this week includes new study results on DAXI, expanding systemic therapies for psoriasis, COVID-19 induced skin challenges, plus more.

Weekly Roundup: January 4-8, 2021

Continued research has led to the development of many systemic therapeutic agents for the treatment of plaque psoriasis, including a growing list of novel biologics. These innovative biologic agents are proving to be safe and effective in addressing moderate to severe psoriasis disease, offering hope to this patient population. 

Affecting approximately 7 million individuals in the United States and 125 million worldwide, psoriasis is a chronic inflammatory skin disease that is typically characterized by scaly indurated erythematous plaques commonly located on the scalp, trunk and extensor surfaces. It can significantly impact quality of life and have far-reaching psychosocial implications in some patients. The pathogenesis of psoriasis stems from the dysregulation of the immune system, resulting in chronic inflammation and uncontrolled keratinocyte proliferation. 

Beyond the cutaneous manifestations, psoriasis is also recognized as a systemic disease and is associated with many systemic comorbidities, including psoriatic arthritis, Crohn’s disease, uveitis, obesity, type II diabetes mellitus, dyslipidemia, hypertension, and cardiovascular issues, as well as anxiety and depression. As such, the goal is to find effective treatments that can achieve and maintain a high clearance of psoriatic lesions and address the potential mosaic of comorbidities with minimal side effects.

For patients with mild psoriasis, topical agents remain the mainstay of treatment and include topical corticosteroids, vitamin D analogues, calcineurin inhibitors, and keratolytics. For those with moderate to severe psoriasis, biologics are considered first-line therapy.

The recognition of psoriasis as an auto-inflammatory disease heralded the use of systemic biological agents for treatment. It is widely viewed that the advent of the biologics in psoriasis therapy has brought promising treatment solutions to those patients suffering from moderate to severe psoriatic disease. 

There are several systemic therapies currently available for patients suffering from moderate to severe psoriasis and psoriatic arthritis, including cyclosporine, methotrexate, apremilast, and retinoids, traditionally used to suppress the immune system and keratinocyte proliferation. However, biologic agents including inhibitors to tumor necrosis factor α (TNF-α) such as etanercept, infliximab, and adalimumab, interleukin (IL)-12 and IL-23 inhibitor ustekinumab, IL-17A inhibitors secukinumab and ixekizumab, IL-17RA inhibitor brodalumab, and IL-23 inhibitors guselkumab, risankizumab, tildrakizumab, and mirikizumab are just part of a growing list of tools available in the dermatologist’s armamentarium and have generated much interest among clinicians and their psoriasis patients.

Advancements in the immunopathogenesis of psoriasis have identified IL-23 and IL-17 as fundamental contributors in the immune pathways of the disease. According to a recent review paper

, the discovery of the IL-23/T17 signaling pathway as well as the significant therapeutic advances made of late, including novel biologic therapies, have led to an improved treatment and management of psoriatic disease. 

“The discovery of the roles for interleukin-17 (IL-17) and IL-23 on the development of psoriatic disease has led to substantial increases in our understanding of the pathogenic immune events in psoriasis and has led to a paradigm shift in the treatment of this condition,” write study authors Jason J. Krueger, M.D., Ph.D., Professor and Senior Physician, Director, the Milstein Research Program, Laboratory Head, Investigative Dermatology, The Rockefeller University, New York, N.Y., and colleagues.

The FDA recently approved several inhibitors of the IL-23/IL-17 signaling axis for the treatment of psoriasis, which, according to the researchers, have proven to be very effective, resulting in significant improvements in approximately 80%-90% of psoriasis patients.

“The unprecedented success of selective IL-17 and IL-23 antagonists for the treatment of psoriasis underscores the essential nature of these cytokines in the pathogenesis of this chronic inflammatory condition,” write study authors.

, Ellis et al. appraised two network meta-analyses that assessed systemic therapies for patients with moderate to severe psoriasis and found that the newer biologic therapies targeting the IL-12/23 and IL-17 axes appear to be more effective than older biologics and oral agents. 

Several clinical trials have shown novel biologic agents such as ixekizumab and guselkumab to be highly effective for patients with moderate to severe psoriasis

. Recently approved by the FDA as the first selective IL-23 inhibitor for the treatment of psoriatic arthritis, guselkumab is a human IgG1λ monoclonal antibody targeting the p19 subunit of IL-23, while ixekizumab is a human monoclonal antibody targeting IL-17A. 

In a recent head-to-head study in which researchers compared the efficacy, safety and speed of response of the two biologics

, 1,027 patients with moderate to severe psoriasis were randomized to receive the approved dose of either subcutaneous ixekizumab or guselkumab with the primary end point of 100 percent improvement in the PASI (PASI 100) score at 12 weeks follow-up. Results showed that ixekizumab was superior to guselkumab for quickly improving signs and symptoms of moderate to severe psoriasis. The primary end point PASI 100 at week 12 was met [215/520 ixekizumab (41%); 126/507 guselkumab (25%)]. According to the study investigators, ixekizumab can offer complete skin clearance more rapidly to patients with moderate to severe psoriasis when compared to guselkumab, the IL-23 inhibitor. 

Other head-to-head clinical trials of secukinumab versus ustekinumab

, and brodalumab versus ustekinumab11 have demonstrated the superior efficacy of the IL-17 antagonists. 

In another network meta-analysis study including 77 trials (34,816 patients)

, investigators assessed the relative efficacy of IL-17 and IL-23 targeted treatments for moderate to severe psoriasis, comparing the short-term efficacy of available (or imminently available) biologic and non-biologic systemic therapies for the disease, reflected in the PASI response following treatments. Results showed that brodalumab, ixekizumab, secukinumab, guselkumab, and risankizumab were superior in efficacy to tildrakizumab, ustekinumab, all the TNF-α inhibitors, and non-biologic systemic treatments for the treatment of psoriasis. In terms of PASI 90 and PASI 100 response, data showed that brodalumab, ixekizumab, guselkumab, and risankizumab demonstrated the greatest therapeutic benefits. 

There are an increasing number of selectively targeting biologic agents that clinicians have at their disposal to better treat and manage their patients with moderate to severe psoriasis patients; however, individual characteristics vary, including the rapidity of onset, long-term-efficacy, safety profile and effects on comorbidities. Finding the ideal systemic therapy for patients with moderate to severe psoriasis and navigating among the many different and novel biologic agents can be a daunting task. Having a better understanding of each drug’s individual characteristics can help guide clinicians towards the best therapeutic choice for their psoriasis patients, resulting in minimizing disease impact and higher patient satisfaction and quality of life. 

1. Armstrong AW, Read C. Pathophysiology, clinical presentation, and treatment of psoriasis: a review. JAMA. 2020; 323(19): 1945-1960. doi: 10.1001/jama.2020.4006

2. Hawkes JE, Yan BY, Chan TC, Krueger JG. Discovery of the IL-23/IL-17 signaling pathway and the treatment of psoriasis. Immunol. 2018; 201(6): 1605-1613. doi: 10.4049/jimmunol.1800013

3. Ellis AG, Flohr C, Drucker AM. Network meta-analyses of systemic treatments for psoriasis: a critical appraisal: Original Articles: Jabbar-Lopez ZK, Yiu ZZN, Ward V et al. Quantitative evaluation of biologic therapy options for psoriasis: a systematic review and network meta-analysis. J Invest Dermatol. 2017; 137:1646-54. Sbidian E, Chaimani A, Garcia-Doval I et al. Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis. Cochrane Database Syst Rev 2017; 12:CD011535. Br. J. Dermatol. 2019; 180: 282–288. 

4. Griffiths CE, Reich K, Lebwohl M, van de Kerkhof P, Paul C, Menter A, et al. Comparison of ixekizumab with etanercept or placebo in moderate-to-severe psoriasis (UNCOVER-2 and UNCOVER-3): results from two phase 3 randomised trials. Lancet. 2015; 386(9993): 541-551. doi: 10.1016/S0140-6736(15)60125-8

5. Paul C, Griffiths CEM, van de Kerkhof PCM, Puig L, Dutronc Y, Henneges C, et al. Ixekizumab provides superior efficacy compared with ustekinumab over 52 weeks of treatment: Results from IXORA-S, a phase 3 study. JAAD. 2019; 80: 70–79. doi: 10.1016/j.jaad.2018.06.039

6. Reich K, Griffiths CEM, Gordon KB, Papp KA, Song M, Randazzo B, et al. Maintenance of clinical response and consistent safety profile with up to 3 years of continuous treatment with guselkumab: Results from the VOYAGE 1 and VOYAGE 2 trials. JAAD. 2019; 82(4):936-945, doi: 10.1016/j.jaad.2019.11.040

7. Blauvelt A, Papp KA, Griffiths CE, Randazzo B, Wasfi Y, Shen YK, et al. Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the continuous treatment of patients with moderate to severe psoriasis: Results from the phase III, double-blinded, placebo- and active comparator-controlled VOYAGE 1 trial. JAAD. 2017; 76: 405–417 

8. Blauvelt A, Papp K, Gottlieb A, et al. A head-to-head comparison of ixekizumab vs. guselkumab in patients with moderate-to-severe plaque psoriasis: 12-week efficacy, safety and speed of response from a randomized, double-blinded trial. Br J Dermatol. 2020; 182(6): 1348-1358. doi: 10.1111/bjd.18851. Epub 2020 Jan 15

9. Blauvelt A, Reich K, Tsai TF, Tyring S, Vanaclocha F, et al. Secukinumab is superior to ustekinumab in clearing skin of subjects with moderate-to-severe plaque psoriasis up to 1 year: results from the CLEAR study. JAAD.2017. 76: 60-69 

10. Gordon KB, Blauvelt A, Papp KA, Langley RG, Luger T, Ohtsuki M, et al. Phase 3 trials of ixekizumab in moderate-to-severe plaque psoriasis. N Engl J Med. 2016. 375: 345–356

11. Lebwohl M, Strober B, Menter A, Gordon K, Weglowska J, Puig L, et al. Phase 3 studies comparing brodalumab with ustekinumab in psoriasis. N Engl J Med. 2015. 373: 1318–1328

12. Sawyer LM, Malottki K, Sabry-Grant C, Yasmeen N, Wright E, Sohrt A, et al. Assessing the relative efficacy of interleukin-17 and interleukin-23 targeted treatments for moderate-to-severe plaque psoriasis: A systematic review and network meta-analysis of PASI response. PLoS ONE. 2019; 14: e0220868-10. doi: 10.1371/journal.pone.0220868

Expanding line of therapeutic agents for psoriasis 

The American Society for Dermatologic Surgery (ASDS) has released a guidance regarding COVID-19 vaccine side effects in dermal filler patients, titled “Guidance Regarding SARS-CoV-2 mRNA Vaccine Side Effects in Dermal Filler Patients.”

The guidance provides data from the U.S. Food and Drug Administration (FDA) on reactions from the mRNA vaccine and shares insight for practitioners and patients in relation to the occurrence of reactions based on the latest data available.

“Patient safety is foremost in the practice of dermatology and board certified dermatologists take adverse effects seriously,” says Mathew Avram, MD, JD, ASDS president. “Although still very early in the vaccination process, this guidance is meant to be informational and helpful as we move forward during pandemic recovery efforts.”

In the guidance, FDA data reports show three participants out of 15,184 who received at least one dose of Moderna’s mRNA-1273 vaccine have developed lip for facial swelling in areas of dermal filler placement, while no participants in the placebo group experienced any filler-related adverse events.

regarding dermal fillers and the vaccine are as follows:

Dermal filler inflammatory events very seldom occur with both hyaluronic acid and non-hyaluronic acid fillers.

Evidence suggests these reactions can be immunologically triggered by viral and bacterial illness, vaccinations (i.e., influenza vaccine) and dental procedures.

These rare adverse events are temporary and respond to treatments such as oral corticosteroids and hyaluronidase, and often times resolve without treatment.

Patients already treated with dermal fillers should not be discouraged or precluded from receiving vaccines of any kind. Patients who have had vaccines should not be precluded from receiving dermal fillers in the future.

In the Moderna mRNA-1273 trial, three reactions were possibly related to dermal fillers out of 15,184 vaccine recipients. It is unknown how many subjects in the trial had previous treatment with dermal fillers.

ASDS members should obtain a pertinent medical history on all patients.

Dermal fillers should be administered by board-certified physicians who are experts in both the injection of dermal fillers and management of complications arising from them.

In addition to this guidance, members of the Soft-tissue Fillers Guideline Task also plan on publishing a multispecialty clinical guideline on the prevention and treatment of SARS-CoV-2 mRNA vaccine-related adverse events from soft tissue fillers.

More information on the guidance from ASDS can be found 

1. ASDS Provides Guidance Regarding SARS-CoV-2 mRNA Vaccine Side Effects. (2020, December 28). Retrieved January 07, 2021, from 

https://www.prweb.com/releases/asds_provides_guidance_regarding_sars_cov_2_mrna_vaccine_side_effects_in_dermal_filler_patients/prweb17636524.htm

Avram, M., Bertucci, V., Cox, S., Jones, D., & Mariwalla, K. (2020, December 28). Guidance 2. Regarding SARS-CoV-2 mRNA Vaccine Side Effects in Dermal Filler Patients. Retrieved January 07, 2021, from 

https://www.asds.net/Portals/0/PDF/secure/ASDS-SARS-CoV-2-Vaccine-Guidance.pdf

Revance Therapeutics announces the results from its phase 2 multicenter, open-label study investigating DaxibotulinumtoxinA (DAXI) as an injectable treatment for glabellar lines, lateral canthal lines and dynamic forehead lines.

The study examined the efficacy of DAXI in 48 patients over 36 weeks, in which participants were given a single treatment of 40 units DAXI in the glabella, 32 units in the forehead and 48 units split between the lateral canthi.

At week 4, 100% of participants reported being “somewhat satisfied” with the treatment in all three areas using a 7-point Subject Global Satisfaction with Treatment Questionnaire. A total of 83%, 78.7% and 80.9% of participants reported being “very satisfied” with the treatment of their glabellar lines, forehead lines and lateral canthal lines, respectfully.

“Many of my patients are looking for a more enduring treatment of their upper facial lines and wrinkles, as currently available neuromodulators typically only last 10 to 16 weeks, depending on the location within the face,” says Jeffrey S. Dover, MD, FRCPC, study investigator and co-director of SkinCare Physicians in Chestnut Hill, Mass. “I am pleased to see the high patient satisfaction scores for DaxibotulinumtoxinA for Injection and expect a treatment regimen of just two times a year could be a welcome benefit to patients looking for long-lasting treatment.”

Investigators conclude DAXI is safe for injection and well-tolerated when used in the glabella, lateral canthi and forehead. The most common adverse events were injection site erythema (6.3%), facial discomfort (4.2%) and headache (2.1 %), and no treatment-related serious adverse events were reported.

Revance Therapeutics announces positive results from its phase 2 multicenter, open-label study investigating DaxibotulinumtoxinA (DAXI) as an injectable treatment for glabellar lines, lateral canthal lines and dynamic forehead lines